What is the recommended regimen for vitamin D (Vitamin D3) replacement in individuals with vitamin D deficiency?

Vitamin D Replacement for Deficiency

For vitamin D deficiency (<20 ng/mL), the recommended regimen is 50,000 IU of vitamin D2 or D3 once weekly for 8 weeks, followed by a maintenance dose of 800-2000 IU daily. 1

Initial Treatment Based on Deficiency Severity

• For vitamin D deficiency (<20 ng/mL), start with a loading dose of 50,000 IU vitamin D2 once weekly for 8 weeks 1
• For severe deficiency (<10-12 ng/mL), use the same regimen of 50,000 IU weekly but extend to 8-12 weeks to ensure adequate repletion 1
• In critically ill patients with measured low plasma levels (25-hydroxy-vitamin D < 12.5 ng/ml or 50 nmol/l), a high single dose of vitamin D3 (500,000 IU) can be administered within a week after admission 2
• Each 1,000 IU of vitamin D supplementation typically increases serum 25(OH)D levels by approximately 10 ng/mL, though individual responses vary significantly 1

Maintenance Phase

• After completing the loading dose regimen, transition to a maintenance dose of 800-2000 IU daily 1
• For patients with malabsorption or obesity, higher maintenance doses may be required (2000-4000 IU daily) 1
• Vitamin D3 (cholecalciferol) is preferred over vitamin D2 (ergocalciferol) for maintenance therapy, especially when using intermittent dosing regimens 1
• Evidence suggests that 2,000 IU daily may be insufficient to maintain levels above 30 ng/mL in some patients, particularly those with higher BMI 3

Alternative Dosing Regimens

• For patients who prefer less frequent dosing, 50,000 IU monthly or 100,000 IU every 3 months are effective maintenance options 1
• Daily dosing is physiologically more natural, but monthly dosing with vitamin D3 has similar effects on 25(OH)D concentrations 1
• For elderly patients (≥65 years), institutionalized individuals, and those with dark skin or limited sun exposure, supplementation with 800 IU/day can be initiated without baseline testing 1

Monitoring Response to Treatment

• Measure 25(OH)D levels after at least 3 months of supplementation to allow serum levels to reach plateau 1
• Target 25(OH)D level should be at least 30 ng/mL (75 nmol/L) for optimal health benefits, particularly for anti-fracture efficacy 1, 4
• The upper safety limit for 25(OH)D is considered to be 100 ng/mL (250 nmol/L) 1
• If using an intermittent regimen (weekly, monthly), measurement should be performed just prior to the next scheduled dose 4

Special Considerations

• For patients with chronic kidney disease, vitamin D supplementation is particularly important as kidney disease increases deficiency risk 1
• For patients with malabsorption syndromes (e.g., celiac disease), higher doses may be required and more frequent monitoring is recommended 1
• In patients with malabsorptive conditions, intramuscular (IM) vitamin D administration may be more effective than oral supplementation 4
• Therapeutic dosage should be readjusted as soon as there is clinical improvement, with individualized dosing based on patient response 5

Important Caveats

• Vitamin D supplementation benefits are primarily seen in those with documented deficiency, not in the general population with normal levels 1
• Calcium intake should be assessed alongside vitamin D supplementation, with recommended daily intake of 1000-1500 mg 1
• Vitamin D toxicity is rare but can occur with prolonged high doses (typically >10,000 IU daily), causing hypercalcemia, hypercalciuria, and renal issues 1
• When high therapeutic doses are used, progress should be followed with frequent blood calcium determinations to prevent toxicity 5
• Mineral oil interferes with the absorption of fat-soluble vitamins, including vitamin D preparations 5
• Administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with vitamin D may cause hypercalcemia 5

Factors Affecting Vitamin D Response

• Significant factors affecting the change in serum concentrations of 25-hydroxyvitamin D, in addition to the dose administered, include starting serum concentration of 25(OH)D, body mass index (BMI), age, and serum albumin concentration 6
• The recommended daily allowance for vitamin D is often inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients 6
• About 5000 IU vitamin D3/day is usually needed to correct deficiency in many patients, and the maintenance dose should be ≥2000 IU/day 6, 7